A large number of ion-selective solvent polymeric or liquid membrane electrodes have been developed during the last decades. A comprehensive list of such electrodes described up to 1990 can be found in Umezawa, Handbook of Ion-Selective Electrodes: Selectivity Coefficients; CRC Press: Boca Raton, Ann Arbor, Boston, 1990. Such potentiometric sensors are widely used in clinical analyzers.
The basis of the response is a selective recognition of the target ion, e.g., by selective complexing by a lipophilic ligand, also called an ionophore. In its uncomplexed form, the ionophore may be electrically neutral (neutral ionophore) or charged (charged ionophore). Also ion-exchangers not capable of specific interactions with the target ion can be applied. It must be noted, that the presence of at least traces of ion exchanger is mandatory if an electrically neutral ionophore is used.
The membranes are typically based on a polymer such as polyvinyl chloride (PVC) or a polyurethane and usually also contain a water immiscible organic liquid which has plasticizer properties. However, none of the latter components is mandatory and both membranes without a polymer and polymer membranes without a plasticizer are known. Occasionally, some or all of the relevant components are covalently bonded to the polymer.
The present invention applies to all of the aforementioned types of ion-selective membrane electrodes. Other types of ion-selective electrodes are based on a sparingly soluble salt, such as silver halogenide or on glass (e.g., pH glass electrode). The present invention does not apply to these latter types of membranes.
In order to measure the potential; the membrane must be assembled into an electric circuit. One surface of the membrane contacts the sample solution while the other surface is electrically connected, via internal reference, to the potentiometric measurement equipment, which is further connected through a reference electrode to the sample solution. The internal reference may be a solid member, which directly contacts the ion-selective membrane. Examples of such a solid contact are platinum, platinum covered by a polypyrrole, graphite, or a chlorinated silver wire. On the other hand, the membrane can be directly deposited on a field effect transistor. So far, most commonly an electrolyte is applied at the inner membrane side, which is contacted to a reference electrode such as Ag/AgCl.
In spite of varying designs, the detection limit of practically all ion-selective solvent polymeric or liquid membrane electrodes is on the order of 10.sup.-6 M. For many applications, such as clinical analysis of a series of physiologically relevant ions, this if of no concern, but this detection limit prohibits the use of such electrodes for environmental monitoring of toxic heavy metal ions such as Pb.sup.2+, Cd.sup.2+, Cu.sup.2+, Ag.sup.+ and/or Hg.sup.2+ because they should be detected at the submicromolar level. For example, the U.S. Environmental Protection Agency (EPA) (U.S. Environmental Protection Agency Office of Water and Hazardous Materials, Quality Criteria for Water, U.S. GPO; Washington, D.C., 1976) and the World Health Organization (World Health Organization, Guidelines for Drinking Water Quality, Vol. I; Recommendations; WHO; Geneva, 1984) tolerate a maximum amount of 0.05 mg of lead/L drinking water, which corresponds to a concentration of 2.4 10.sup.-7 M Pb.sup.2+. This level is below the detection limit of available ion-selective electrodes. The tolerated concentrations of other toxic ions of concern are at submicromolar concentrations as well. Another application, not feasible with the present technology is the analysis of physiologically relevant trace metal ions such as Zn.sup.2+ in clinical samples.
In general, the detection limit of an ion-selective electrode can be caused by the presence of an interfering ion. However, detection limits around 10.sup.-6 M are also found in absence of such interferences. In such cases, there is no fundamental reason why the detection limit should not be much lower. Although the exact reason for the lack of much lower detection limits of such liquid membrane electrodes is not proven, it is believed that the primary ions leaching out of the membrane phase might be limiting. As a result, the local ion activity at the membrane surface (Nernstian boundary layer) is kept at a higher level independently of the concentration of the bulk sample.
This interpretation was suggested by the fact that lower detection limits below 10.sup.-6 M could be observed if the concentration of the measuring ions was buffered in the sample by using an ion buffer such as ethylenediamine tetraacetic acid (EDTA) or nitrillotriacetic acid. For example detection limits of 10.sup.-9 M have been reported for Ca.sup.2+ (cf. Schefer, U.; Ammann, D.; Pretsch, E.; Oesch, U.; Simon, W. Neutral Carrier Based Ca.sup.2+ -Selective Electrode with Detection Limit in the Sub-Nanomolar Range. Anal. Chim. Acta 1986, 58, 2282-2285) and Pb.sup.2+ (cf. Bakker, E.; Willer, M.; Pretsch, E. Detection limits of ion-selective bulk optodes and corresponding electrodes. Anal. Chim. Acta 1993, 282, 265-271) with such ion buffers. Such experiments are, however, only of academic interest because practically relevant samples do not contain any ion buffers.
Although these results make it likely that the higher than expected detection limits are caused by the ions leaching out of the membrane, the exact reason of this leaching process is not known. In the comprehensive standard reference volume on ion-selective electrodes Morf, W. E. The Principles of Ion-Selective Electrodes and of Membrane Transport, Elsevier; N.Y., 1981, various mechanisms are discussed for solid membrane electrodes (pp. 171-183) but the topic is not treated for solvent polymeric or liquid membrane electrodes. In the case of a Pb.sup.2+ selective electrode, experiments were made with various concentrations of the inner reference electrolyte. It was however found that "The replacement of the inner filling electrolyte of the electrode by a solution buffered to 1.3.times.10.sup.-7 M Pb.sup.2+ did not significantly lower the detection limit" (cf. Bakker, E.; Willer, M.; Pretsch, E. Detection limits of ion-selective bulk optodes and corresponding electrodes. Anal. Chim. Acta 1993, 282, 265-271).
The idea that the interfering ions originate from the inner reference electrolyte is also disproved by the fact that no lower detection limits were reported with solid contact electrodes or with ion-selective field effect transistors which do not contain such an internal reference solution (see also Example 5). Thus according to present knowledge it was not expected that the detection limit of ion-selective electrodes would be influenced by the inner reference system.